Showing papers by "Patrick R. Hof published in 2006"
TL;DR: It is proposed that the anterior cingulate cortex is a specialization of neocortex rather than a more primitive stage of cortical evolution, and thus are a recent evolutionary specialization probably related to these functions central to intelligent behavior.
Abstract: We propose that the anterior cingulate cortex is a specialization of neocortex rather than a more primitive stage of cortical evolution. Functions central to intelligent behavior, that is, emotional self-control, focused problem solving, error recognition, and adaptive response to changing conditions, are juxtaposed with the emotions in this structure. Evidence of an important role for the anterior cingulate cortex in these functions has accumulated through single-neuron recording, electrical stimulation, EEG, PET, fMRI, and lesion studies. The anterior cingulate cortex contains a class of spindle-shaped neurons that are found only in humans and the great apes, and thus are a recent evolutionary specialization probably related to these functions. The spindle cells appear to be widely connected with diverse parts of the brain and may have a role in the coordination that would be essential in developing the capacity to focus on difficult problems. Furthermore, they emerge postnatally and their survival may be enhanced or reduced by environmental conditions of enrichment or stress, thus potentially influencing adult competence or dysfunction in emotional self-control and problem-solving capacity.
918 citations
TL;DR: This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.
Abstract: Stressful life events have been implicated clinically in the pathogenesis of mental illness, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of these psychiatric conditions are associated with structural and functional abnormalities in a network of prefrontal cortical structures. Here, we examine whether chronic stress-induced dendritic alterations in the medial prefrontal cortex (mPFC) and orbital frontal cortex (OFC) underlie impairments in the behaviors that they subserve. After 21 d of repeated restraint stress, rats were tested on a perceptual attentional set-shifting task, which yields dissociable measures of reversal learning and attentional set-shifting, functions that are mediated by the OFC and mPFC, respectively. Intracellular iontophoretic injections of Lucifer yellow were performed in a subset of these rats to examine dendritic morphology in layer II/III pyramidal cells of the mPFC and lateral OFC. Chronic stress induced a selective impairment in attentional set-shifting and a corresponding retraction (20%) of apical dendritic arbors in the mPFC. In stressed rats, but not in controls, decreased dendritic arborization in the mPFC predicted impaired attentional set-shifting performance. In contrast, stress was not found to adversely affect reversal learning or dendritic morphology in the lateral OFC. Instead, apical dendritic arborization in the OFC was increased by 43%. This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.
870 citations
TL;DR: It is estimated that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress, indicating that dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired.
Abstract: The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and in the regulation of stress-induced hypothalamic--pituitary--adrenal (HPA) activity. Here we examined the effect of repeated restraint stress on dendritic spine number in the medial PFC. Rats were perfused after receiving 21 days of daily restraint stress, and intracellular iontophoretic injections of Lucifer Yellow were carried out in layer II/III pyramidal neurons in the anterior cingulate and prelimbic cortices. We found that stress results in a significant (16%) decrease in apical dendritic spine density in medial PFC pyramidal neurons, and confirmed a previous observation that total apical dendritic length is reduced by 20% in the same neurons. We estimate that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress. A decrease in medial PFC dendritic spines may not only be indicative of a decrease in the total population of axospinous synapses, but may impair these neurons’ capacity for biochemical compartmentalization and plasticity in which dendritic spines play a major role. Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired.
757 citations
TL;DR: This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample and finds mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%.
Abstract: Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V (CW)), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 microm in controls and 25.7 microm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity.
467 citations
TL;DR: Analysis of glia–neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions have not evolved differentially higher requirements for metabolic support.
Abstract: Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia-neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia-neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as "theory of mind" (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.
326 citations
TL;DR: Results document that, although the aged primate PFC is vulnerable in the absence of factors such as circulating estrogens, it remains responsive to long-term cyclic 17β-estradiol treatment, and that increased dendritic spine density and altered spine morphology may contribute to the cognitive benefits of such treatment.
Abstract: Long-term cyclic treatment with 17beta-estradiol reverses age-related impairment in ovariectomized rhesus monkeys on a test of cognitive function mediated by the prefrontal cortex (PFC). Here, we examined potential neurobiological substrates of this effect using intracellular loading and morphometric analyses to test the possibility that the cognitive benefits of hormone treatment are associated with structural plasticity in layer III pyramidal cells in PFC area 46. 17beta-Estradiol did not affect several parameters such as total dendritic length and branching. In contrast, 17beta-estradiol administration increased apical and basal dendritic spine density, and induced a shift toward smaller spines, a response linked to increased spine motility, NMDA receptor-mediated activity, and learning. These results document that, although the aged primate PFC is vulnerable in the absence of factors such as circulating estrogens, it remains responsive to long-term cyclic 17beta-estradiol treatment, and that increased dendritic spine density and altered spine morphology may contribute to the cognitive benefits of such treatment.
244 citations
TL;DR: It is demonstrated that Megaptera differs from Odontoceti in certain aspects of cortical cytoarchitecture and may provide a neuromorphologic basis for functional and behavioral differences between the suborders as well as a reflection of their divergent evolution.
Abstract: Cetaceans diverged from terrestrial mammals between 50 and 60 million years ago and acquired, during their adaptation to a fully aquatic milieu, many derived features, including echolocation (in odontocetes), remarkable auditory and communicative abilities, as well as a complex social organization. Whereas brain structure has been documented in detail in some odontocetes, few reports exist on its organization in mysticetes. We studied the cerebral cortex of the humpback whale (Megaptera novaeangliae) in comparison to another balaenopterid, the fin whale, and representative odontocetes. We observed several differences between Megaptera and odontocetes, such as a highly clustered organization of layer II over the occipital and inferotemporal neocortex, whereas such pattern is restricted to the ventral insula in odontocetes. A striking observation in Megaptera was the presence in layer V of the anterior cingulate, anterior insular, and frontopolar cortices of large spindle cells, similar in morphology and distribution to those described in hominids, suggesting a case of parallel evolution. They were also observed in the fin whale and the largest odontocetes, but not in species with smaller brains or body size. The hippocampal formation, unremarkable in odontocetes, is further diminutive in Megaptera, contrasting with terrestrial mammals. As in odontocetes, clear cytoarchitectural patterns exist in the neocortex of Megaptera, making it possible to define many cortical domains. These observations demonstrate that Megaptera differs from Odontoceti in certain aspects of cortical cytoarchitecture and may provide a neuromorphologic basis for functional and behavioral differences between the suborders as well as a reflection of their divergent evolution.
226 citations
TL;DR: This protocol describes a versatile shape analysis algorithm, Rayburst sampling, that generates automated 3D measurements from LSM images that provides a primitive for the development of higher level algorithms that solve specific shape analysis problems.
Abstract: Precise quantification of complex three-dimensional (3D) structures from laser scanning microscopy (LSM) images is increasingly necessary in understanding normal function and pathologic processes in biology. This protocol describes a versatile shape analysis algorithm, Rayburst sampling, that generates automated 3D measurements from LSM images. Rayburst defines and efficiently casts a multidirectional core of rays from an interior point to the surface of a solid, allowing precise quantification of anisotropic and irregularly shaped 3D structures. Quantization error owing to the finite voxel representation in digital images is minimized by interpolating intensity values continuously between voxels. The Rayburst algorithm provides a primitive for the development of higher level algorithms that solve specific shape analysis problems. Examples are provided of applications to 3D neuronal morphometry: (i) estimation of diameters in tubular neuronal dendritic branching structures, and (ii) measurement of volumes and surface areas for dendritic spines and spatially complex histopathologic structures.
199 citations
TL;DR: In rats with 95% lesion of the BF cholinergic neurons, AD levels in the BF did not increase with 6 h of prolonged waking, and the selective adenosine A1 receptor agonist N6-cyclohexyladenosine, administered to the BF, continued to be effective in inducing sleep, indicating that the BF dendritic neurons are not essential to sleep induction.
Abstract: It is currently hypothesized that the drive to sleep is determined by the activity of the basal forebrain (BF) cholinergic neurons, which release adenosine (AD), perhaps because of increased metabolic activity associated with the neuronal discharge during waking, and the accumulating AD begins to inhibit these neurons so that sleep-active neurons can become active. This hypothesis grew from the observation that AD induces sleep and AD levels increase with wake in the basal forebrain, but surprisingly it still remains untested. Here we directly test whether the basal forebrain cholinergic neurons are central to the AD regulation of sleep drive by administering 192-IgG-saporin to lesion the BF cholinergic neurons and then measuring AD levels in the BF. In rats with 95% lesion of the BF cholinergic neurons, AD levels in the BF did not increase with 6 h of prolonged waking. However, the lesioned rats had intact sleep drive after 6 and 12 h of prolonged waking, indicating that the AD accumulation in the BF is not necessary for sleep drive. Next we determined that, in the absence of the BF cholinergic neurons, the selective adenosine A1 receptor agonist N6-cyclohexyladenosine, administered to the BF, continued to be effective in inducing sleep, indicating that the BF cholinergic neurons are not essential to sleep induction. Thus, neither the activity of the BF cholinergic neurons nor the accumulation of AD in the BF during wake is necessary for sleep drive.
176 citations
TL;DR: These findings, consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions.
127 citations
TL;DR: The data reveal a dissociation between the patterns of progression of NFT and neuronal loss in the entorhinal cortex and CA1 field and show that less than 50% of the cognitive variability may be attributable to AD neuronal pathology in these areas.
TL;DR: Changes in capillary morphometric parameters may represent independent predictors of AD-related neuronal depletion and cognitive decline, and are consistent with the growing interest in brain aging.
Abstract: The presence of microvascular changes has been documented both in brain aging and Alzheimer disease (AD), although the relationship between the morphometry of brain capillaries and cognitive impairment is still unknown. We performed an analysis of capillary morphometric parameters and AD-related pathology in 19 elderly individuals with variable degrees of cognitive decline. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale. Total capillary lengths and numbers as well as mean length-weighted diameter, total neurofibrillary tangle (NFT) and neuron numbers, and amyloid volume were estimated in entorhinal cortex and the CA1 field. Total capillary numbers and mean diameters explained almost 40% of the neuron number variability in both the CA1 and entorhinal cortex. Total capillary length and numbers in the CA1 and entorhinal cortex did not predict cognitive status. Mean capillary diameters in the CA1 and entorhinal cortex were significantly related to CDR scores, explaining 18.5% and 31.1% of the cognitive variability, respectively. This relationship persisted after controlling for NFT and neuron numbers in multivariate regression models. Consistent with the growing interest about microvascular pathology in brain aging, the present data indicate that changes in capillary morphometric parameters may represent independent predictors of AD-related neuronal depletion and cognitive decline.
TL;DR: An overview of clinicopathological analyses in patients with atypical progression of AD symptomatology is provided with special reference to the relationship between specific cognitive and behavioral deficits and hierarchical patterns of AD lesion distribution within the cerebral cortex.
TL;DR: This study expands on previous findings by exploring the topography of minicolumnar abnormalities in autism by finding an interaction of diagnosis and region for peripheral neuropil space for frontopolar region and anterior cingulate gyrus.
TL;DR: Observations suggest an expanded and diversified organization of the prelunate gyrus in some cercopithecoids that may reflect adaptation to specific ecological environments.
Abstract: Anatomical and electrophysiological studies have revealed a complex organization in the macaque prelunate gyrus. We investigated the morphology and architecture of the prelunate gyrus in Old World monkeys. In Macaca nemestrina, we observed a sulcus crossing the prelunate gyrus within 2 mm of the vertical meridian representation. In other macaque species and other cercopithecines, we observed substantial variations in sulcal morphology across the prelunate gyrus. We did not find a sulcus in all species, and the location and depth of that indentation on the gyrus varied among species. A deep sulcus was observed in all species that emerged earlier in evolution than macaques, such as guenons, baboons, and colobines. We analyzed the regional and parcellation features of the prelunate gyrus in three macaque species, M. maura, M. mulatta, and M. radiata, and in Erythrocebus patas, with emphasis on the relation of structure to the distribution of prelunate visual areas. Nonphosphorylated neurofilament protein immunoreactivity permitted the delineation of a novel area in the prelunate gyrus of Old World monkeys, located around the prelunate sulcus. Species-specific patterns were also observed in the prelunate gyrus of the patas monkey compared to macaques. These observations, as well as a cladistic analysis of the data, suggest an expanded and diversified organization of the prelunate gyrus in some cercopithecoids that may reflect adaptation to specific ecological environments. It was, however, progressively lost in most macaques, being retained only in species that diverged early in the evolution of the genus Macaca, such as M. nemestrina and M. maura. Anat Rec Part A, 288A:753–775, 2006. © 2006 Wiley-Liss, Inc.
TL;DR: In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, highIQ was associated with less worry, and in all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores.
Abstract: We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR) MRSI scans that were obtained from an earlier [Mathew, SJ, Mao, X, Coplan, JD, Smith, EL, Sackeim, HA, Gorman, JM, Shungu, DC, 2004 Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI) Serial multislice/multivoxel MRSI scans had been performed on a 15-T MRI Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence These conclusions are deemed preliminary due to small sample size, with further study of cerebral WM in anxiety disorders suggested
TL;DR: The authors examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabeling procedure to visualize the spine-associated protein spinophilin.
Abstract: Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine-associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin-immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory.
TL;DR: This work aims to demonstrate the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals, not necessarily belonging to the same breeds.
Abstract: CHET C. SHERWOOD,a,b,c RALPH L. HOLLOWAY,a,c PATRICK J. GANNON,c,d KATERINA SEMENDEFERI,e JOSEPH M. ERWIN,f KARL ZILLES,g AND PATRICK R. HOFb,c,f aDepartment of Anthropology, Columbia University, New York, New York 10027, USA bKastor Neurobiology of Aging Laboratory and Fishberg Research Center for Neurobiology, and dDepartment of Otolaryngology, Mount Sinai School of Medicine, New York, New York 10029, USA cNew York Consortium in Evolutionary Primatology, New York, New York eDepartment of Anthropology, University of California, San Diego, La Jolla, California 92093-0532, USA fFoundation for Comparative and Conservation Biology, Needmore, Pennsylvania 17238, USA gInstitut fur Medizin, Forschungszentrum Julich und C.& O. Vogt-Institut fur Hirnforschung, Heinrich-Heine-Universitat, Dusseldorf, Germany
Book•
01 Oct 2006
TL;DR: The role of Hormesis in Life Extension by Dietary Restriction and Fasting have a Long-Term Anticarcinogenic Effect?
Abstract: Preface The Role of Hormesis in Life Extension by Dietary Restriction: Masoro, E.J. Metabolic Reprogramming in Dietary Restriction: Anderson, R.M. Weindruch, R. Secrets of the Iac Operon. Glucose Hysteresis as a Mechanism in Dietary Restriction, Aging and Disease: Mobbs, C.V. Mastaitis, J.W. Zhang, M. Isoda, F. Cheng, H. Yen, K. Effects of Dietary Restriction on the Expression of Insulin-Signaling-Related Genes in Long-Lived Mutant Mice: Bartke, A. Masternak, M.M. Al-Regaiey, K.A. Bonkowski, M.S. Anti-Inflammatory Mechanisms of Dietary Restriction in Slowing Aging Processes: Morgan, T.E. Wong, A.M. Finch, C.E. Dietary Restriction in the Nematode Caenorhabditis elegans: Houthoofd, K. Gems, D. Johnson, T.E. Vanfleteren, J.R. Diet Restriction in Drosophila melanogaster. Design and Analysis: Tatar, M. Dietary Restriction in Aging Nonhuman Primates: Mattison, J.A. Roth, G.S. Lane, M.A. Ingram, D.K. Caloric Intake and Alzheimer's Disease. Experimental Approaches and Therapeutic Implications: Pasinetti, G.M. Zhao, Z. Qin, W. Ho, L. Shrishailam, Y. MacGrogan, D. Ressmann, W. Humala, N. Liu, X. Romero, C. Stetka, B. Chen, L. Ksiezak-Reding, H. Wang, J. Can Short-Term Dietary Restriction and Fasting Have a Long-Term Anticarcinogenic Effect?: Klebanov, S. Author Index Subject Index.
TL;DR: The new 3D scaling exponents introduced in this study permit efficient morphometric characterization of complex dendritic arbors in the fewest possible parameters, that can be directly related to their electrotonic properties, and hence to neuronal function.
TL;DR: It is demonstrated that the LC‐EC technique may be used to investigate the modulation of the synthesis and release of retinal DA in vitro, without the prior uptake of radiolabelled transmitter.
Abstract: The basal catecholamine content of rabbit retina was determined by liquid chromatography with electrochemical detection (LC-EC) and 3,4-dihydroxyphenylethylamine (dopamine, DA) found to be the major catecholamine. The immediate DA precursor, 3,4-dihydroxyphenylalanine (L-DOPA), and the metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were also detected at about 2.8% and 17% of DA levels, respectively. When added exogenously, L-tyrosine did not increase the rate of DA synthesis over the basal level. In contrast, exogenous L-DOPA led to a 3.5-fold increase in DA, and to a 20-fold increase in DOPAC content. The monoamine oxidase inhibitors pargyline and (-)-deprenyl differentially affected the degradation of DA, since 100 microM pargyline was apparently more effective than 100 microM (-)-deprenyl. Reserpine and (+/-)-amphetamine each induced a Ca2+-independent decrease of DA stores. The separate actions of reserpine and (+/-)-amphetamine in lowering tissue DA levels were additive, suggesting two separate pools of DA available for release from presynaptic stores. The present study demonstrates that the LC-EC technique may be used to investigate the modulation of the synthesis and release of retinal DA in vitro, without the prior uptake of radiolabelled transmitter.